PROJECT SUMMARY The Resource Support Core (RSC) will provide infrastructure and tools to enable a cohesive approach to the collection, analysis, storage and sharing of data across the SCORE projects. The RSC will also provide expert support in areas such as biostatistics, transcutaneous vagus nerve stimulation, and advance autonomic and neuroimaging analyses. Establishing a unified approach enhances the quality of all studies, allowing each project to inform the others in potentially significant ways, and enabling valuable exploratory analyses through the pooling of data collected by multiple projects. The noninvasive nature of MRI allows for multiple experiments on an individual subject, either during the course of one examination period or on multiple occasions, as proposed in the current proposal to accomplish the aims of projects 1 and 2. The imaging data must be registered accurately, in both space and time, and interpreted to isolate physiological phenomena of interest from extraneous noise sources. Three-dimensional, high-resolution, anatomical MRI images will provide the basis for interrelating neuroimaging information. A broad range of functional imaging analytic tools will then be applied to interrogate both resting brain state and task- and/or stimulus-induced regional activation. The image analysis tools we propose have been extensively tested and validated by investigators at the Athinoula A. Martinos Center for Biomedical Imaging, over many years. The RSC will provide access to this broad neuroimaging expertise of the Martinos Center and will deliver a reproducible and efficient means to obtain, analyze, test and correlate structural and functional neuroimaging with physiological data. The RSC will also provide support on biomedical signal processing by developing and executing plans for advanced mathematical modeling and processing of physiological measurements taken in both the animal and human experiments. This will facilitate translational analyses of the mechanisms of autonomic dysregulation explored in projects 1 and 3. Experts on the implementation of non-invasive vagus nerve stimulation techniques in human and animal models have been included in the RSC and will assist in the experimental set up and interpretation of vagal neuromodulation effects on behavioral, imaging and physiological outcomes in projects 2 and 3. Beyond acquisition and analytic support, the RSC is designed to support critical cross-project data analyses. Cross-project synergy is essential to the overall SCORE research plan and built into the design of the projects. This will allow for interesting and potentially valuable pooled analyses of the data and will permit us to address larger-scale questions about sex differences in the neuroscience of the neural pathophysiological mechanisms responsible for autonomic dysregulation in major depression and sex differences in the effects of a novel transcutaneous vagal stimulation technique on the attenuation of these alterations.